ArticlePloS one2011
Endothelin receptor A antagonism attenuates renal medullary blood flow impairment in endotoxemic pigs.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Does kidney function in experimental porcine sepsis fulfill the RIFLE criteria for acute kidney injury? A systematic review.Frontiers in physiology · 2026Pooled it
- Experimental models of acute kidney injury for translational research.Nature reviews. Nephrology · 2022Review
- The Development of a Juvenile Porcine Augmented Renal Clearance Model Through Continuous Infusion of Lipopolysaccharides: An Exploratory Study.Frontiers in veterinary science · 2021Article
- B-type natriuretic peptide is upregulated by c-Jun N-terminal kinase and contributes to septic hypotension.JCI insight · 2020Article
- C-terminal proendothelin-1 (CT-proET-1) is associated with organ failure and predicts mortality in critically ill patients.Journal of intensive care · 2017Article
- Nur77 attenuates endothelin-1 expression via downregulation of NF-κB and p38 MAPK in A549 cells and in an ARDS rat model.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- Adrenomedullin and endothelin-1 are associated with myocardial injury and death in septic shock patients.Critical care (London, England) · 2016Article
- Long-term sequelae from acute kidney injury: potential mechanisms for the observed poor renal outcomes.Critical care (London, England) · 2015Review
- The role of endothelin-1 and endothelin receptor antagonists in inflammatory response and sepsis.Archivum immunologiae et therapiae experimentalis · 2015Review
- Progressive endothelin-1 gene activation initiates chronic/end-stage renal disease following experimental ischemic/reperfusion injury.Kidney international · 2013Article
- Endothelin antagonists in hypertension and kidney disease.Pediatric nephrology (Berlin, Germany) · 2013Review
- Pharmacological targets in the renal peritubular microenvironment: implications for therapy for sepsis-induced acute kidney injury.Pharmacology & therapeutics · 2012Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEndothelin-1 is a potent endogenous vasoconstrictor that contributes to renal microcirculatory impairment during endotoxemia and sepsis. Here we investigated if the renal circulatory and metabolic effects of endothelin during endotoxemia are mediated through activation of endothelin-A receptors. METHODS AND
findingsA randomized experimental study was performed with anesthetized and mechanically ventilated pigs subjected to Escherichia coli endotoxin infusion for five hours. After two hours the animals were treated with the selective endothelin receptor type A antagonist TBC 3711 (2 mg⋅kg(-1), n = 8) or served as endotoxin-treated controls (n = 8). Renal artery blood flow, diuresis and creatinine clearance decreased in response to endotoxemia. Perfusion in the cortex, as measured by laser doppler flowmetry, was reduced in both groups, but TBC 3711 attenuated the decrease in the medulla (p = 0.002). Compared to control, TBC 3711 reduced renal oxygen extraction as well as cortical and medullary lactate/pyruvate ratios (p<0.05) measured by microdialysis. Furthermore, TBC 3711 attenuated the decline in renal cortical interstitial glucose levels (p = 0.02) and increased medullary pyruvate levels (p = 0.03). Decreased creatinine clearance and oliguria were present in both groups without any significant difference.
conclusionsThese results suggest that endothelin released during endotoxemia acts via endothelin A receptors to impair renal medullary blood flow causing ischemia. Reduced renal oxygen extraction and cortical levels of lactate by TBC 3711, without effects on cortical blood flow, further suggest additional metabolic effects of endothelin type A receptor activation in this model of endotoxin induced acute kidney injury.
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